Is NEBL p.Ala769= (c.2307T>C) pathogenic?

NEBL p.Ala769= (c.2307T>C) is classified Benign/Likely benign in NEBL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0441%, nfe); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Ala769= (c.2307T>C)?

NEBL p.Ala769= (c.2307T>C) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Ala769= (c.2307T>C) in the general population?

NEBL p.Ala769= (c.2307T>C) is ultra-rare (popmax 0.0441%, nfe) (gnomAD).

NEBL p.Ala769=

c.2307T>C · rs144815863 · VCV201899

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, nfe)

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.3, phastCons 1
Overall
CADD	8.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0441% European (non-Finnish) · 519/1,176,944 alleles

Filtering AF 0.041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0397%

Overall 0.0327% 527/1,610,756 alleles · ultra-rare exomes 501/1,458,420 · genomes 26/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0441%	2,268
Remaining individualsnot grpmax-eligible	0.00801%	12,479
African / African-American	0.004%	24,998

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: NEBL
Protein: p.Ala769=
Coding: c.2307T>C
MANE Select: NM_006393
dbSNP: rs144815863
Type: single nucleotide variant
Location: chr10:20813978 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB

Full NEBL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEBL p.Ala769Val Uncertain significance ★ ⚠ same residue
NEBL c.1227+5G>A Uncertain significance ★★ same condition
NEBL c.1870-1G>A Uncertain significance ★★ same condition
NEBL c.798+1G>A Uncertain significance ★★ same condition
NEBL c.903+1G>T Uncertain significance ★★ same condition
NEBL p.Ala114Ser Uncertain significance ★★ ⚠ same condition
NEBL p.Ala219Thr Uncertain significance ★★ ⚠ same condition
NEBL p.Ala264Val Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nebl-p-ala769 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown